Clot Risk Higher with In Vitro Pregnancy

Action Points

Note that this Swedish cross-sectional study revealed an association between in-vitro fertilization and venous or pulmonary embolism.

Be aware that the rate of thrombosis in the IVF group was quite low at 0.42%.

Women who become pregnant through in vitro fertilization are at increased risk for venous thromboembolism and pulmonary embolism, particularly during the first trimester, a Swedish cross-sectional study found.

Compared with women who had natural pregnancies, those with in vitro fertilization had four times the risk of venous thromboembolism in the first 3 months of pregnancy (HR 4.05, 95% CI 2.54 to 6.46), according to Peter Henriksson, MD, PhD, and colleagues from the Karolinska Institute in Stockholm.

And the risk of pulmonary embolism was nearly seven times higher during those first 12 weeks (HR 6.97, 95% CI 2.21 to 21.96), the researchers reported online in BMJ.

"Doctors should be aware of these increased risks because the symptoms of pulmonary embolism can be insidious and the condition is potentially fatal," they cautioned.

The occurrence of venous thromboembolism during natural pregnancy is well recognized, but uncertainty has persisted as to the risks following in vitro fertilization.

Accordingly, Henriksson and colleagues compared embolic events among 23,498 women in the Swedish in vitro fertilization registry with events in 116,960 age- and calendar year-matched controls.

They found a rate of venous thromboembolism in the in vitro group of 4.2 per 1,000, compared with a rate of 2.5 per 1,000 among controls.

The risk was increased when the pregnancy was considered as a whole, though not to the extent seen for the first trimester (HR 1.77, 95% CI 1.41 to 2.23).

But unlike the elevated risk in the first trimester, no increase was seen in the second (HR 95% CI 0.51 to 1.97) or the third (HR 1.04, 95% CI 0.64 to 1.69) trimesters.

No differences in risk for venous thromboembolism were seen between the two groups before the pregnancy or in the year following the birth.

The rates of pulmonary embolism for the in vitro and control groups were 8.1 per 10,000 and 6 per 10,000, respectively, with an overall hazard ratio during the pregnancy of 1.42 (95% CI 0.86 to 2.36).

As with venous thromboembolism, no increased risk was seen for pulmonary embolism during trimester two (HR 0.42, 95% CI 0.05 to 3.20) or three (HR 0.40, 95% CI 0.10 to 1.68).

The finding of the highest risk being in the early months of pregnancy may relate to elevated estrogen, which is a known risk factor for thromboembolism.

"A plausible initiator of adverse mechanisms could be the noticeable increase in endogenous estrogen levels during the stimulation phase of treatment before the actual procedure," they explained.

Unlike women with natural pregnancies, no increase in risk for venous thromboembolism was seen according to body mass index (BMI) in the women who had in vitro fertilization.

A possible explanation for this was that ovarian hyperstimulation is associated with venous thromboembolism and occurs more frequently among women with low BMI, the researchers suggested.

Additional multivariate analyses with stratification by BMI below or above 25 and adjusting for factors including smoking, maternal age and education, calendar year, and parity did not significantly alter the first trimester thromboembolism risk associated with in vitro pregnancy (HR 4.22, 95% CI 2.46 to 7.26).

The researchers noted that it was important to adjust for factors such as age and calendar year, because women having in vitro fertilization tend to be older, and risk of thromboembolism rises with increasing age.

Also, the procedures used for in vitro fertilization have been refined over time, and the incidence of thromboembolism in pregnancy overall has risen during the past decade.

This increased incidence could reflect clinicians' heightened awareness of the condition and widespread use of ultrasound, and the researchers acknowledged that their inability to measure these factors was a limitation of their analysis.

An additional limitation was the inclusion only of women with successful deliveries, which does not account for severe events including maternal fatalities.

"Efforts should focus on the identification of women at risk of thromboembolism, with prophylactic anticoagulation considered in women planning to undergo in vitro fertilization," they concluded.

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